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目的构建氯化镍腹腔注射染毒大鼠的生理毒代动力学(physiologically based toxicokinetic,PBTK)模型,估计氯化镍染毒后不同脏器的组织分配系数,外推构建职业人群呼吸道一次性镍暴露的PBTK模型,预测镍暴露后其在人体内的分布特征。方法通过构建大鼠氯化镍染毒PBTK模型并结合大鼠镍染毒后的矢量数据,应用Acslx软件对镍染毒后大鼠不同组织器官的分配系数进行拟合,外推建立职业人群呼吸道暴露镍的PBTK模型。结果构建了大鼠氯化镍腹腔注射染毒的PBTK模型,估计出镍在大鼠不同脏器的组织分配系数,分别是肾/血分配系数最高为0.668,肺/血分配系数为0.102,脾/血分配系数为0.037,肝/血分配系数为0.028,心/血分配系数为0.022,脑/血分配系数最低为0.006。外推构建了职业人群呼吸道暴露0.1 mg/m~3镍8 h的PBTK模型,结果显示肾脏中镍含量最高,8 h高达3.328μg/kg,其次是脾脏(0.185μg/kg)、肝脏(0.140μg/kg)和心脏(0.110μg/kg),脑中含量最低为0.030μg/kg,肾脏为镍离子主要的代谢器官。结论 PBTK模型能够较好地预测镍在职业人群体内的分布特征,阐明镍分布的时间-内剂量关系。
Objective To construct a model of physiologically based toxicokinetic (PBTK) model of intraperitoneal injection of nickel chloride in mice and estimate the tissue partition coefficient of different organs after nickel chloride exposure. Exposed PBTK model to predict the distribution of nickel in the human body after exposure. Methods The model of PBTK was established by nickel chloride injection in rats and the vector data of nickel exposure were used. Acslx software was used to fit the distribution coefficients of different tissues and organs of rats after nickel exposure. Exposed nickel PBTK model. Results The PBTK model was established by intraperitoneal injection of nickel chloride in rats. The tissue distribution coefficients of nickel in different organs of rats were estimated. The highest coefficient of renal / blood partition coefficient was 0.668, the pulmonary / blood partition coefficient was 0.102, / Blood partition coefficient was 0.037, liver / blood partition coefficient was 0.028, heart / blood partition coefficient was 0.022, and brain / blood partition coefficient was the lowest 0.006. The PBTK model was constructed by extrapolation of occupational exposure to 0.1 mg / m ~ 3 Ni for 8 h. The results showed that the highest content of nickel in kidney was 3.328 μg / kg at 8 h, followed by spleen (0.185 μg / kg) and liver μg / kg) and heart (0.110 μg / kg), the lowest content in the brain was 0.030 μg / kg. The kidney was the main metabolic organ of nickel ion. Conclusions The PBTK model can predict the distribution of nickel in the occupational population and clarify the time-to-dose relationship of nickel distribution.